The object of the proposed research is to apply recently developed methods for forming beta-lactams to the synthesis of antibiotics in the beta-lactam field. Beta-Lactams will also be employed as intermediates in the synthesis of macrocyclic lactams. It has recently been found that systems markedly different in structure from the penicillins and cephalosporins containing bicyclic nuclei (thienamycin) and a monocyclic nucleus (nocardicins) show pronounced biological activity. Our objective is to use methods which we have recently developed for the synthesis of these antibiotics, particularly the carbopenem systee present in thienomycin. In this work we will explore new routes to the formation of (3.2.0)azaheptenes present in the thienamycin such as the Diels Alder addition of 1,4-dienes to azetines, followed by suitable ring contraction. Work on this aspect of the research will require the development of new methods for the formation of azetine carboxylates or of suitable precursors capable of yielding the unsaturated four-membered unit in situ. A third aspect of the research will be aimed at the use of substituted beta-lactams as intermediates in the formation of the spermidine alkaloids. Among these macrocyclic systems, celacinnine and dihydroperiphylline contain thirteen-membered lactams, and homaline contains two eight-membered lactam rings. Our plan is to utilize the intramolecular ring opening of beta-lactams for the construction of these large rings. In our synthetic scheme, attachment of suitable diamino residues to the nitrogen atom of the azetidinone will permit construction of the macrocyclic lactam by intramolecular amide exchange.